Efficacy and Toxicity Analysis of Capecitabine and Temozolomide in Neuroendocrine Neoplasms

View More View Less
  • 1 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: The capecitabine/temozolomide (CAPTEM) regimen has significant activity in advanced neuroendocrine tumors (NETs). Questions exist regarding activity in pancreatic versus nonpancreatic NETs, risk of opportunistic infections, long-term myelotoxicity, and safety of prolonged treatment duration. Analysis of large patient cohorts is needed for the evaluation of rare toxicities and assessment of risk factors. Methods: We conducted a retrospective study of all patients with advanced NETs seen at Moffitt Cancer Center between January 2008 and June 2019 who received treatment with CAPTEM. Results: A total of 462 patients were eligible. The objective radiographic response rate was 46%, and the disease control rate was 81%. Median progression-free survival (PFS) was 18 months (95% CI, 14.0–21.9 months) and median overall survival was 51 months (95% CI, 42.8–59.2 months): 62 months in well-differentiated NETs versus 14 months in poorly differentiated neuroendocrine carcinomas (P<.0001). Patients with primary pancreatic tumors had the highest partial response rates and longest median PFS. Incidences of grade 4 thrombocytopenia and neutropenia were 7% and 3%, respectively, and substantially higher in women than men (P=.02 and P=.004, respectively). Only 1 case (0.2%) of suspected Pneumocystis pneumonia (PCP) was observed in a patient receiving corticosteroids. Three patients developed myelodysplastic disease, all of whom had received prior peptide receptor radiotherapy (PRRT). There were no acute treatment-related deaths; 1 patient died 2 months after a thrombocytopenic bleed. Conclusions: The CAPTEM regimen is exceptionally safe. Efficacy is particularly robust in well-differentiated pancreatic NETs. Severe myelotoxicity is rare; the risk of grade 4 cytopenias is significantly increased in women, and therefore sex-based dosing should be considered. There were no cases of myelodysplastic syndromes, except among patients who had received PRRT, a known risk factor. The risk of PCP is negligible.

Submitted August 3, 2020; final revision received December 4, 2020; accepted for publication January 27, 2021. Published online August 24, 2021.

Author contributions: Study concept and design: Al-Toubah, Strosberg. Data acquisition: All authors. Data analysis and interpretation: Al-Toubah, Strosberg. Treatment of patients: Valone, Haider, Strosberg. Manuscript preparation: Al-Toubah, Strosberg.

Disclosures: Ms. Valone has disclosed serving as a consultant for Lexicon and serving on speakers’ bureaus for Lexicon, Ipsen, and Novartis. Dr. Strosberg has disclosed serving as a consultant for Novartis and serving on speakers’ bureaus for Ipsen and Lexicon. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Jonathan R. Strosberg, MD, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa FL 33612. Email: jonathan.strosberg@moffitt.org

Supplementary Materials

    • Supplemental Materials (PDF 536 KB)
  • 1.

    Cives M, Ghayouri M, Morse B, et al. Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. Endocr Relat Cancer 2016;23:759767.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Kunz PL, Catalano PJ, Nimeiri H, et al. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: a trial of the ECOG-ACRIN Cancer Research Group (E2211) [abstract]. J Clin Oncol 2018;36(Suppl):Abstract 4004.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Strosberg JR, Fine RL, Choi J, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 2011;117:268275.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Chatzellis E, Angelousi A, Daskalakis K, et al. Activity and safety of standard and prolonged capecitabine/temozolomide administration in patients with advanced neuroendocrine neoplasms. Neuroendocrinology 2019;109:333345.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Fine RL, Gulati AP, Krantz BA, et al. Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: the Pancreas Center at Columbia University experience. Cancer Chemother Pharmacol 2013;71:663670.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Al-Toubah T, Morse B, Strosberg J. Capecitabine and temozolomide in advanced lung neuroendocrine neoplasms. Oncologist 2020;25:e4852.

  • 7.

    Owen DH, Alexander AJ, Konda B, et al. Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O6-methylguanine DNA methyltransferase as a biomarker for response. Oncotarget 2017;8:104046104056.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Papaxoinis G, Kordatou Z, McCallum L, et al. Capecitabine and temozolomide in patients with advanced pulmonary carcinoid tumours. Neuroendocrinology 2020;110:413421.

  • 9.

    Saranga-Perry V, Morse B, Centeno B, et al. Treatment of metastatic neuroendocrine tumors of the thymus with capecitabine and temozolomide: a case series. Neuroendocrinology 2013;97:318321.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    De Vos FY, Gijtenbeek JM, Bleeker-Rovers CP, et al. Pneumocystis jirovecii pneumonia prophylaxis during temozolomide treatment for high-grade gliomas. Crit Rev Oncol Hematol 2013;85:373382.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Schwarzberg AB, Stover EH, Sengupta T, et al. Selective lymphopenia and opportunistic infections in neuroendocrine tumor patients receiving temozolomide. Cancer Invest 2007;25:249255.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Bhatia S. Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 2013;40:666675.

  • 13.

    Parghane RV, Ostwal V, Ramaswamy A, et al. Long-term outcome of “sandwich” chemo-PRRT: a novel treatment strategy for metastatic neuroendocrine tumors with both FDG- and SSTR-avid aggressive disease. Eur J Nucl Med Mol Imaging 2021;48:913923.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Chan D, Bergsland EK, Chan JA, et al. Temozolomide in grade III neuroendocrine neoplasms (G3 NENs): a multicenter retrospective review [abstract]. J Clin Oncol 2019;37(Suppl):Abstract 321.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Spada F, Maisonneuve P, Fumagalli C, et al. Temozolomide alone or in combination with capecitabine in patients with advanced neuroendocrine neoplasms: an Italian multicenter real-world analysis. Endocrine 2021;72:268278.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Thomas K, Voros BA, Meadows-Taylor M, et al. Outcomes of capecitabine and temozolomide (CAPTEM) in advanced neuroendocrine neoplasms (NENs). Cancers (Basel) 2020;12:206.

    • Crossref
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 435 435 435
PDF Downloads 219 219 219
EPUB Downloads 0 0 0